Naimovičius Lukas, Miroshnichenko Mila, Opar Ekin, Hölzel Helen, Morikawa Masa-Aki, Kimizuka Nobuo, Dapkevičius Manvydas, Lekavičius Justas, Radiunas Edvinas, Kazlauskas Karolis, Cilleros-Mañé Víctor, Riefolo Fabio, Matera Carlo, Harmandar Kevser, Taniguchi Masahiko, Dumoulin Fabienne, Lindsey Jonathan S, Bharmoria Pankaj, Gorostiza Pau, Moth-Poulsen Kasper
Institute of Materials Science of Barcelona, ICMAB-CSIC, Bellaterra, Barcelona, Spain.
Institute of Photonics and Nanotechnology, Vilnius University, Vilnius, Lithuania.
Nat Commun. 2025 Jul 10;16(1):6377. doi: 10.1038/s41467-025-61301-3.
Red, far red, or near-infrared photoswitchable drugs offer immense photo-pharmacological advantages due to the higher light penetration through the skin. Such photoactivation is achieved using processes such as two- and three-photon absorption, excited-state absorption, and triplet-triplet annihilation upconversion, which require higher photon fluences (W to kW cm) than the resilience constraints of skin (200 mW cm). Herein, a generalized approach of cis-to-trans photoisomerization of azobenzenes is demonstrated via triplet sensitization with NIR-I illumination (850 nm) of a new Zn-octa-substituted phthalocyanine photosensitizer, in aqueous medium at 2.62 mW cm. The approach is applied to control the heart rate of a frog tadpole via cis-to-trans photoisomerization of an azobenzene-functionalized muscarinic acetylcholine receptor M agonist in the phototherapeutic window (730 nm excitation: 42 mW cm). This advance highlights a powerful photo-pharmacological strategy for modulation of in vivo activity at 2-4 orders of magnitude lower photon fluences of NIR light compared to established methods.
由于红光、远红光或近红外光在皮肤中的穿透性更强，可光开关药物具有巨大的光药理学优势。这种光激活是通过双光子吸收、三光子吸收、激发态吸收和三线态-三线态湮灭上转换等过程实现的，这些过程所需的光子通量（W至kW/cm²）高于皮肤的耐受极限（200 mW/cm²）。在此，我们展示了一种通用方法，即在水介质中，通过用新型锌八取代酞菁光敏剂在850 nm近红外光照射下进行三线态敏化，实现偶氮苯的顺反式光异构化，光通量为2.62 mW/cm²。该方法应用于通过在光治疗窗口（730 nm激发：42 mW/cm²）中对偶氮苯功能化的毒蕈碱型乙酰胆碱受体M激动剂进行顺反式光异构化来控制青蛙蝌蚪的心率。这一进展突出了一种强大的光药理学策略，与现有方法相比，该策略可在近红外光光子通量低2至4个数量级的情况下调节体内活性。
